The physiological and pathological reactions of the body to stress are very important clinically. Gastric and duodenal ulcers are quite common, and they are especially prone to occur and persist in stressful environments. Dopamine has been implicated in healing processes within the gastrointestinal tract; but the source of the dopamine was unknown. Last year we determined that the pancreas synthesizes dopamine and releases it into the duodenum. Using immunohistochemistry, in situ hybridization, histochemistry, Western blotting, RT-PCR, and radioactive uptake studies, we also localized a source of dopamine in the gastric mucosa. Thus, dopamine may serve as a protective agent in the stomach as well as the intestinal lumen. The molecular target of gastrointestinal dopamine appears to be the D1b receptor. This suggests that a specific agonist to this receptor might prove useful in treating mucosal injuries. We started to use a model, where the dopamine D5 receptor was genetically lacking (D5 ko mice) to study the role of this receptor in the mucosal defense. We use ulcerogenic agents and study the development of gastric and duodenal ulcers in control and knockout mice.